Functional imaging for medical diagnostics has been used for decades. In some functional imaging methods, e.g. PET (positron emission tomography) or SPECT (single-photon emission computed tomography) peptides such as Edotreotid (DOTATOC) are marked with radionuclides such as 68Gallium and used as radiopharmaceuticals (also referred to as tracers). When introduced into the human body the radiopharmaceutical binds to certain receptors which are particularly numerous in tumor cells. The functional imaging can detect and localize the increased beta-plus-decay of the 68Gallium. According to [I. Velikyan: Synthesis, Characterisation and Application of 68Ga-labelled Macromolecules. Dissertation, University Uppsala, 2005] the isotope 68Gallium decays with a radioactive half-life of 67.629 minutes in a proportion of 89% by emitting a positron with at most 1.9 MeV and of 11% by catching electrons; thereby respectively creating the daughter isotope 68Zink. In nuclear medical applications the emitted positron hits an electron after travelling a few millimeters so that both annihilate and create two photons with 511 keV each, wherein both photons are emitted at a relative angle of nearly 180° from the point of annihilation. The emitted photons can be detected by appropriate detectors. Reconstructing a number of detection events allows for quite precisely localising the point of annihilation.
Due to the short half-life of 68Gallium, the radiopharmaceutical cannot be shelved over long time periods but has to be prepared at relatively short notice prior to the intended application.
68Gallium is generated by means of so called 68Gallium-generators, also referred to as 68Ge/68Ga-generators, from 68Germanium. 68Germanium has a half life of 270.8 days and decays into the daughter isotope 68Gallium, which concentrates in the generator until reaching a cut-off concentration determined by its own decay. The generated 68Gallium is eluted by a solvent fed into the generator. The solvent eluting only Gallium but not Germanium, separates Gallium out of the stationary phase from the parent isotope 68Germanium.
Known methods use hydrochloric acid with a normality from 0.05 N to 0.4 N for elution, wherein the elution volume is between 5 ml and 10 ml. The eluate is therefore hydrochloric and cannot be directly used for labelling peptides.
This problem has been tackled by different approaches.
In a method known as anionic concentration, the eluate is mixed with a large volume of concentrated hydrochloric acid, 68Ga is then collected by an anion exchanger and subsequently eluted by means of water into a HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer solution for labelling peptides or other ligands. This method requires a subsequent purification of the product, i.e. separation of unwanted substances. Furthermore, the method requires handling of large quantities of concentrated hydrochloric acid.
Another established method is the combined cationic/anionic concentration, wherein a cation exchange cartridge (SCX—strong cation exchanger) and an anion exchange cartridge (SAX—strong anion exchanger) are used.
In the cationic concentration of 68Gallium the 68Gallium is collected using a cation exchanger (SCX) and subsequently eluted with an acetone/hydrochloric acid solution. The obtained reaction mixture therefore contains acetone which has to be removed by distilling at temperatures of more than 90° C. prior to application of the product to the human body. The use of acetone requires additional quality control testing of the final product such as gas chromatography.
There remains a need for a kit for improved preparation of a radiopharmaceutical and for a respectively improved method for preparation of a radiopharmaceutical.